Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders



Walters, Raymond K, Polimanti, Renato, Johnson, Emma C, McClintick, Jeanette N, Adams, Mark J, Adkins, Amy E, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah
et al (show 158 more authors) (2018) Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nature Neuroscience, 21 (12). pp. 1656-1669.

[img] Text
PGC_alcdep_maintext.pdf - Author Accepted Manuscript

Download (623kB)
[img] Text
PGC_alcdep_SI.pdf - Author Accepted Manuscript

Download (584kB)

Abstract

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Item Type: Article
Uncontrolled Keywords: 23andMe Research Team, Humans, Alcoholism, Genetic Predisposition to Disease, Mental Disorders, Genotype, Phenotype, Polymorphism, Single Nucleotide, Alleles, Genome-Wide Association Study
Depositing User: Symplectic Admin
Date Deposited: 08 Jan 2019 15:20
Last Modified: 19 Jan 2023 01:08
DOI: 10.1038/s41593-018-0275-1
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3030546